Hydroquinone Exposure Worsens Rheumatoid Arthritis through the Activation of the Aryl Hydrocarbon Receptor and Interleukin-17 Pathways

Abstract

Rheumatoid arthritis (RA) development is strongly associated with cigarette smoke exposure, which activates the aryl hydrocarbon receptor (AhR) as a trigger for Th17 inflammatory pathways. We previously demonstrated that the exposure to hydroquinone (HQ), one of the major compounds of cigarette tar, aggravates the arthritis symptomatology in rats. However, the mechanisms related to the HQ-related RA still remain elusive. Cell viability, cytokine secretion, and gene expression were measured in RA human fibroblast-like synoviocytes (RAHFLS) treated with HQ and stimulated or not with TNF-α. Antigen-induced arthritis (AIA) was also elicited in wild type (WT), AhR −/− or IL-17R −/− C57BL/6 mice upon daily exposure to nebulized HQ (25ppm) between days 15 to 21. At day 21, mice were challenged with mBSA and inflammatory parameters were assessed. The in vitro HQ treatment up-regulated TNFR1, TNFR2 expression, and increased ROS production. The co-treatment of HQ and TNF-α enhanced the IL-6 and IL-8 secretion. However, the pre-incubation of RAHFLS with an AhR antagonist inhibited the HQ-mediated cell proliferation and gene expression profile. About the in vivo approach, the HQ exposure worsened the AIA symptoms (edema, pain, cytokines secretion and NETs formation) in WT mice. These AIA effects were abolished in HQ-exposed AhR −/− and IL-17R −/− animals though. Our data demonstrated the harmful HQ influence over the onset of arthritis through the activation and proliferation of synoviocytes. The HQ-related RA severity was also associated with the activation of AhR and IL-17 pathways, highlighting how cigarette smoke compounds can contribute to the RA progression.

Relationship between Antioxidant Activity and Ligand Basicity in the Dipicolinate Series of Oxovanadium(IV) and Dioxovanadium(V) Complexes

“…The four complex compounds were synthesized: (1) 1). The complexes (1)-( 3) are known in the literature [21,22].…”

“…The human body has many defense mechanisms that neutralize the harmful effects of reactive oxygen species. Antioxidants play an important role in reducing oxidative damage in the human body [1][2][3][4][5]. These are compounds which, even at a very low concentration, compared to the substrate, can delay or prevent its oxidation.…”

“…In this study, four oxovanadium(IV) and dioxovanadium(V) dipicolinate (dipic) complexes with 1,10-phenanthroline (phen), 2,2 -bipyridyl (bipy) and the protonated form of 2-phenylpyridine (2-phephyH): (1) has been examined by XRD to confirm its structure. All four complexes have been tested towards antioxidant activities by the nitrotetrazolium blue (NBT) method against the superoxide anion.…”

Hydroquinone, a cigarette smoke compound, affects cartilage homeostasis through activation of the aryl hydrocarbon receptor pathway

“…Finally, as HQ can induce the generation of ROS in different biological systems (Heluany et al, 2018b; Heluany et al, 2021; Mao et al, 2019), and the induction of oxidative stress in chondrocytes has been strongly associated with cartilage damage in OA (Henrotin, Bruckner and Pujol, 2003), we tested whether the HQ exposure could influence the production of ROS in BACs cultures. Our data showed that an incubation of chondrocytes with HQ for 24 hours triggered a significant increase in the levels of ROS in comparison to non-stimulated cells (Figure 2I).…”

“…We have recently shown that exposure to HQ aggravated joint damage in experimental animal models of rheumatoid arthritis (RA) through the activation of the aryl hydrocarbon receptor (AhR) pathway by promoting inflammation, an increased influx of immune cells, synovial proliferation and oxidative stress (Heluany et al, 2018a,b; Heluany et al, 2021).…”